TRIM22. A Multitasking Antiviral Factor.
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ABSTRACT:
SUBMITTER: Pagani I
PROVIDER: S-EPMC8391480 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and aimsTRIM5 and TRIM22 are restriction factors involved in innate immune response and exhibit anti-viral activity. Single nucleotide polymorphisms (SNPs) at TRIM5 and TRIM22 genes have shown to influence several viral infections such as human immunodeficiency virus (HIV), hepatitis B, as well as measles and rubella vaccination. The aim of this study is to analyze whether TRIM5 and TRIM22 polymorphisms are associated with liver fibrosis inflammation-related biomarkers and response to pegylated-interferon-alpha plus ribavirin (pegIFNα/RBV) therapy in HIV/hepatitis C virus (HCV) coinfected patients.MethodsA retrospective study was performed in 319 patients who started pegIFNα/RBV therapy. Liver fibrosis stage was characterized in 288 patients. TRIM5 rs3824949 and TRIM22 polymorphisms (rs1063303, rs7935564, and rs7113258) were genotyped using the GoldenGate assay. The primary outcomes were: a) significant liver fibrosis (≥F2) evaluated by liver biopsy or transient elastography (liver stiffness values ≥7.1 Kpa); b) sustained virological response (SVR) defined as no detectable HCV viral load (<10 IU/mL) at week 24 after the end of the treatment. The secondary outcome variable was plasma chemokine levels.ResultsPatients with TRIM5 rs3824949 GG genotype had higher SVR rate than patients with TRIM5 rs3824949 CC/CG genotypes (p = 0.013), and they had increased odds of achieving SVR (adjusted odds ratio (aOR = 2.58; p = 0.012). Patients with TRIM22 rs1063303 GG genotype had higher proportion of significant liver fibrosis than patients with rs1063303 CC/CG genotypes (p = 0.021), and they had increased odds of having significant hepatic fibrosis (aOR = 2.19; p = 0.034). Patients with TRIM22 rs7113258 AT/AA genotype had higher SVR rate than patients with rs7113258 TT genotypes (p = 0.013), and they had increased odds of achieving SVR (aOR = 1.88; p = 0.041). The TRIM22 haplotype conformed by rs1063303_C and rs7113258_A was more frequent in patients with SVR (p = 0.018) and was significantly associated with achieving SVR (aOR = 2.80; p = 0.013). The TRIM5 rs3824949 GG genotype was significantly associated with higher levels of GRO-α (adjusted arithmetic mean ratio ((aAMR) = 1.40; p = 0.011) and MCP-1 (aAMR = 1.61; p = 0.003).ConclusionsTRIM5 and TRIM22 SNPs are associated to increased odds of significant liver fibrosis and SVR after pegIFNα/RBV therapy in HIV/HCV coinfected patients. Besides, TRIM5 SNP was associated to higher baseline levels of circulating biomarkers GRO and MCP-1.
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Project description:Ulcerative colitis (UC) is a common chronic recurrent inflammatory disease, which seriously threatens human life and health. Therefore, the present study aimed to explore the role of tripartite motif‑containing (TRIM)22 in UC and its potential mechanism. C57BL/6 mice and HT‑29 cell models of UC were constructed using 2% dextran sulphate sodium (DSS). The protein and mRNA expression levels were detected by western blotting and reverse transcription‑quantitative PCR, respectively. Cell transfection was performed to overexpress Kruppel‑like factor 2 (KLF2), or knockdown KLF2, TRIM22 and TRIM30 expression. The levels of inflammatory factors were evaluated by enzyme‑linked immunosorbent assays. Cell Counting Kit‑8 and TUNEL staining assay were employed to assess cell viability and apoptosis. Dual‑luciferase reporter assay and chromatin immunoprecipitation assay were performed to determine the binding ability of the TRIM22 promoter to KLF2. The results revealed that DSS increased the expression levels of TRIM22 in HT‑29 cells and TRIM30 in mice. Short hairpin RNA (sh)‑TRIM30 could inhibit the NF‑κB pathway, and reduce the levels of TNF‑α, IL‑6 and IFN‑γ. Furthermore, KLF2 expression was downregulated in the cell model of UC, and the luciferase assay confirmed that the 3' untranslated region of TRIM22 was a direct target of KLF2. The ChIP assay also verified the binding of KLF2 with the TRIM22 promoter. Notably, knockdown of KLF2 reversed the enhancing effects of sh‑TRIM22 on the viability of DSS‑treated HT‑29 cells. In addition, compared with in the DSS + sh‑TRIM22 group, the protein expression levels of phosphorylated (p)‑NF‑κB and p‑IκBα were increased in the DSS + sh‑TRIM22 + sh‑KLF2 group, as were the levels of TNF‑α, IL‑6 and IFN‑γ. In conclusion, TRIM22 was upregulated in DSS‑induced HT‑29 cells. TRIM22 knockdown increased DSS‑induced HT‑29 cell viability and decreased apoptosis and inflammation; this was reversed by knockdown of KLF2. These findings suggested that TRIM22 may promote disease development through the NF‑κB signaling pathway in UC and could be inhibited by KLF2 transcription.
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Project description:Transcriptional response to virus infection in mice lacking type I and type III signaling The transcriptional response to virus infection is thought to be predominantly induced by interferon (IFN) signaling. Here we demonstrate that, in the absence of IFN signaling, an IFN-like transcriptome is still maintained. This transcriptional activity is mediated from IFN-stimulated response elements (ISREs) that bind to both the IFN stimulated gene factor 3 (ISGF3) as well as to IFN response factor 7 (IRF7). Through a combination of both in vitro biochemistry and in vivo transcriptional profiling, we have dissected what constitutes IRF-specific, ISGF3-specific, or universal ISREs. Taken together, the data presented here suggests that IRF7 can induce an IFN-like transcriptome in the absence of type-I or -III signaling and therefore provides a level of redundancy to cells to ensure the induction of the antiviral state. Mouse: Infections were performed in triplicate and lungs from each condition were pooled for total RNA isolation. Human: Analysis of IRF7 transcriptome in U3A cell line was performed in duplicates.
2010-10-15 | E-GEOD-24695 | biostudies-arrayexpress